Endocrine and Oncologic Surgery Research LabHarrison Department of Surgical Research

Brian J. Czerniecki, M.D., Ph.D.

Development of
Dendritic Cell Vaccines
for
Breast Cancer Prevention

We have become one
of the leading groups in the development of dendritic cell (DC) for
the treatment of early breast cancer ductal carcinoma in situ (DCIS).
Since DCIS and invasive breast cancer (IBC) share very similar risk
factors, developing successful immune based therapies for DCIS can
be translated into treatments for IBC and can be used to develop prevention
strategies for breast cancer. We conducted a phase I trial treating
HER-2/neu positive DCIS patients in a neoadjuvant setting with DC
vaccines. We selected HER-2/neu as a target antigen because HER-2/neu
expressing DCIS is associated with greater risk of recurrence, and
as pointed out below we have noted an association between HER-2/neu
expression and the progression to invasive breast cancer. Recently
HER-2/neu expression has also been shown to be expressed in some breast
cancer stem cells. For these reasons we hypothesized that targeting
HER-2/neu in early breast cancer
could be useful for developing vaccines for treatment of DCIS, IBC,
and develop for breast cancer prevention. Preliminary results
were published in Czerniecki et. al Cancer Research 67:1842-52, 2007
and Cancer Res. 67:6531-4 2007. Briefly we documented that
that these vaccines induce immune responses in about 90% of patients
and induce significant loss of HER-2/neu with over 50% of patients
having complete loss of target HER-2/neu and 18% of patients demonstrating
no evidence of DCIS remaining in the breast following vaccination.
A manuscript describing the final results of the trial is about to
be submitted for publication. In addition, we have documented for
the first time that a HER-2/neu vaccine can induce asymptomatic declines
in cardiac function and there is a need to monitor patients’
cardiac function with effective vaccines similar to treatment with
trastuzumab Bahl et. al American Journal of Surgery (In Press). These
studies were funded by the NIH and renewed this past December 2008,
to continue a clinical trial to assess whether we could completely
eradicate disease by conditioning both the local and systemic immune
response using these HER-2/neu pulsed DC vaccines. This trial was
recently opened and is accruing patients.